Background. Diagnostic and prognostic models are typically evaluated with measures of accuracy that do not address clinical consequences. Decision-analytic techniques allow assessment of clinical outcomes but often require collection of additional information and may be cumbersome to apply to models that yield a continuous result. The authors sought a method for evaluating and comparing prediction models that incorporates clinical consequences, requires only the data set on which the models are tested, and can be applied to models that have either continuous or dichotomous results. Method. The authors describe decision curve analysis, a simple, novel method of evaluating predictive models. They start by assuming that the threshold probability of a disease or event at which a patient would opt for treatment is informative of how the patient weighs the relative harms of a false-positive and a false-negative prediction. This theoretical relationship is then used to derive the net benefit of the model across ...

/pdf/decision-curve-analysis-a-novel-method-for-evaluating-53ofa2294x.pdf

Decision curve analysis: a novel method for evaluating prediction models.

2-D
: two-dimensional
3-D
: three-dimensional
5-FU
: 5-fluorouracil
ACE
: angiotensin-converting enzyme
ARB
: angiotensin II receptor blocker
ASE
: American Society of Echocardiography
BNP
: B-type natriuretic peptide
CABG
: coronary artery bypass graft
CAD
: coronary artery

/pdf/2016-esc-position-paper-on-cancer-treatments-and-1bzyne0xi3.pdf

2016 ESC Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines

No abstract available
Keywords: European Society of Cardiology; arrhythmias; cancer therapy; cardio-oncology; cardiotoxicity; chemotherapy; early detection; ischaemia; myocardial dysfunction; surveillance.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/ejhf.654

2016 ESC Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines The Task Force for cancer treatments and cardiovascular toxicity of the European Society of Cardiology (ESC)

The American Society of Clinical Oncology (ASCO) previously published evidencebased guidelines for the treatment of unresectable non–small-cell lung cancer (NSCLC) [1]. ASCO guidelines are updated periodically by the responsible Expert Panel (Appendix) [2]. For the 2003 update, a methodology similar to that applied in the original ASCO practice guidelines for treatment of unresectable NSCLC was used. Pertinent information published from 1996 through March 2003 was reviewed. The MEDLINE database (1996 through October 2002; National Library of Medicine, Bethesda, MD) was searched to identify relevant information from the published literature for this update. A series of searches was conducted using the medical subject headings, “carcinoma, non–small-cell lung,” “diagnostic imaging,” “neoplasm staging,” “mediastinoscopy,” “bone neoplasms,” “brain neoplasms,” “liver neoplasms,” “adrenal gland neoplasms,” “non–small-cell lung cancer,” “radionuclide imaging,” “bisphosphonates,” “radiotherapy,” “smoking,” “chemoprevention,” and the text words “chemotherapy,” “bone scan,” “PET,” and “zoledronic acid.” These terms were combined with the study design–related subject headings or text words “meta-analysis” and “randomized controlled trial.” Search results were limited to human studies and English-language articles. The Cochrane Library was searched in October 2002 using the phrase “lung cancer.” Directed searches based on the bibliographies of primary articles were also performed. Randomized trials published in the literature since October 2002, as well as data presented at ASCO Annual Meetings, were added to the evidence for these guidelines at the discretion of members of the Expert Panel. The entire update committee met once to discuss strategy and assign responsibilities for the update. A writing committee subsequently met to further review the literature searches, collate different sections of the update, and refine the manuscript. A draft update was circulated to the full Expert Panel for review and approval. The final document was also reviewed by ASCO’s Health Services Research Committee and the ASCO Board of Directors. Each recommendation from the 1997 guideline is listed below, and is followed by an updated (2003) recommendation, if applicable. “No change” is indicated if a particular recommendation has not been revised. A summary of the evidence follows thereafter. In order to preserve the framework of the 1997 guideline, information and recommendations regarding major topics, such as fluorodeoxyglucose positron emission tomography (FDGPET), have been divided and distributed to the appropriate section of the text. ASCO considers adherence to these guidelines to be voluntary. The ultimate determination regarding their application is to be made by the physician in light of each From the American Society of Clinical Oncology, Alexandria, VA.

https://ascopubs.org/doi/pdf/10.1200/JCO.2004.09.053

American Society of Clinical Oncology Treatment of Unresectable Non–Small-Cell Lung Cancer Guideline: Update 2003

The literature is reviewed to identify the main clinical and dose-volume predictors for acute and late radiation-induced heart disease. A clear quantitative dose and/or volume dependence for most cardiac toxicity has not yet been shown, primarily because of the scarcity of the data. Several clinical factors, such as age, comorbidities and doxorubicin use, appear to increase the risk of injury. The existing dose-volume data is presented, as well as suggestions for future investigations to better define radiation-induced cardiac injury.

/pdf/radiation-dose-volume-effects-in-the-brain-weug9uqa6a.pdf

Radiation Dose–Volume Effects in the Brain

Purpose: Radiation therapy (RT) for left-sided breast cancer has been associated with cardiac dysfunction. We herein assess the temporal nature and volume dependence of RT-induced left ventricular perfusion defects and whether these perfusion defects are related to changes in cardiac wall motion or alterations in ejection fraction. Methods: From 1998 to 2001, 114 patients were enrolled onto an IRB-approved prospective clinical study to assess changes in regional and global cardiac function after RT for left-sided breast cancer. Patients were imaged 30 to 60 minutes after injection of technetium 99m sestamibi or tetrofosmin. Post-RT perfusion scans were compared with the pre-RT studies to assess for RT-induced perfusion defects as well as functional changes in wall motion and ejection fraction. Two-tailed Fisher’s exact test and the Cochran-Armitage test for linear trends were used for statistical analysis. Results: The incidence of new perfusion defects 6, 12, 18, and 24 months after RT was 27%, 29%, 38%, and 42%, respectively. New defects occurred in approximately 10% to 20% and 50% to 60% of patients with less than 5%, and greater than 5%, of their left ventricle included within the RT fields, respectively (p = 0.33 to 0.00008). The rates of wall motion abnormalities in patients with and without perfusion defects were 12% to 40% versus 0% to 9%, respectively; p values were 0.007 to 0.16, depending on the post-RT interval. Conclusions: Radiation therapy causes volume-dependent perfusion defects in approximately 40% of patients within 2 years of RT. These perfusion defects are associated with corresponding wall-motion abnormalities. Additional study is necessary to better define the long-term functional consequences of RT-induced perfusion defects.

The incidence and functional consequences of RT-associated cardiac perfusion defects

Radiation-induced lung injury.

Purpose To evaluate the clinical and three-dimensional dosimetric parameters associated with esophageal injury after radiotherapy (RT) for non–small-cell lung cancer. Methods and materials The records of 254 patients treated for non–small-cell lung cancer between 1992 and 2001 were reviewed. A variety of metrics describing the esophageal dose were extracted. The Radiation Therapy Oncology Group toxicity criteria for grading of esophageal injury were used. The median follow-up time for all patients was 43 months (range, 0.5–120 months). Logistic regression analysis, contingency table analyses, and Fisher's exact tests were used for statistical analysis. Results Acute toxicity occurred in 199 (78%) of 254 patients. For acute toxicity of Grade 2 or worse, twice-daily RT, age, nodal stage of N2 or worse, and most dosimetric parameters were predictive. Late toxicity occurred in 17 (7%) of 238 patients. The median and maximal time to the onset of late toxicity was 5 and 40 months after RT, respectively. Late toxicity occurred in 2%, 3%, 17%, 26%, and 100% of patients with acute Grade 0, 1, 2, 3, and 4 toxicity, respectively. For late toxicity, the severity of acute toxicity was most predictive. Conclusion A variety of dosimetric parameters are predictive of acute and late esophageal injury. A strong correlation between the dosimetric parameters prevented a comparison between the predictive abilities of these metrics. The presence of acute injury was the most predictive factor for the development of late injury. Additional studies to define better the predictors of RT-induced esophageal injury are needed.

Dosimetric and clinical predictors for radiation-induced esophageal injury

BACKGROUND.

Radiation therapy (RT) to the left breast/chest wall has been linked with cardiac dysfunction. Previously, the authors identified cardiac perfusion defects in approximately 50% to 60% of patients 0.5 to 2 years post-RT. In the current study, they assessed the persistence of these defects 3 to 6 years post-RT.



METHODS.

From 1998 to 2006, 160 patients with left-sided breast cancer were enrolled onto an Institutional Review Board-approved, prospective study. All patients received tangential photons to the left breast/chest wall. Patients had pre-RT and serial post-RT single-photon emission computed tomography (SPECT) scans to assess changes in regional cardiac perfusion, wall motion, and ejection fraction (EF). Forty-four patients had SPECT scans 3 to 6 years post-RT and were evaluable for the current analysis.



RESULTS.

The overall incidence of perfusion defects at 3 years, 4 years, 5 years, and 6 years was 52% (11 of 21 patients), 71% (17 of 24 patients), 67% (12 of 18 patients), and 57% (4 of 7 patients), respectively. The rate of abnormal SPECT scans 3 to 6 years post-RT in patients who had scans at 0.5 to 2 years that were either all abnormal, intermittently abnormal, or all normal was 80%, 67%, and 63%, respectively. The incidence of wall motion abnormalities in patients with or without perfusion defects 3 to 6 years post-RT was low and did not differ statistically (17% vs 7.1%, respectively; P = .65), as was the incidence of reductions in EF of ≥5% (27% vs 36%, respectively; P = .72).



CONCLUSIONS.

The results from this study indicated that RT-induced perfusion defects may persist or initially may appear 3 to 6 years post-RT in a high percentage of patients. However, these defects were not associated with changes in regional wall motion or EF. Additional study will be needed to determine the clinical relevance of these defects. In the meantime, the authors believe that every effort should be made to minimize incidental irradiation of the heart while maintaining adequate coverage of target volumes. Cancer 2007. © 2007 American Cancer Society.

Prospective assessment of radiotherapy-associated cardiac toxicity in breast cancer patients: analysis of data 3 to 6 years after treatment.

Purpose: The aim of this study was to assess the impact of patient-specific factors, left ventricle (LV) volume, and treatment set-up errors on the rate of perfusion defects 6 to 60 months post–radiation therapy (RT) in patients receiving tangential RT for left-sided breast cancer. Methods and Materials: Between 1998 and 2005, a total of 153 patients were enrolled onto an institutional review board–approved prospective study and had pre- and serial post-RT (6–60 months) cardiac perfusion scans to assess for perfusion defects. Of the patients, 108 had normal pre-RT perfusion scans and available follow-up data. The impact of patient-specific factors on the rate of perfusion defects was assessed at various time points using univariate and multivariate analysis. The impact of set-up errors on the rate of perfusion defects was also analyzed using a one-tailed Fisher's Exact test. Results: Consistent with our prior results, the volume of LV in the RT field was the most significant predictor of perfusion defects on both univariate ( p = 0.0005 to 0.0058) and multivariate analysis ( p = 0.0026 to 0.0029). Body mass index (BMI) was the only significant patient-specific factor on both univariate ( p = 0.0005 to 0.022) and multivariate analysis ( p = 0.0091 to 0.05). In patients with very small volumes of LV in the planned RT fields, the rate of perfusion defects was significantly higher when the fields set-up "too deep" (83% vs. 30%, p = 0.059). The frequency of deep set-up errors was significantly higher among patients with BMI ≥25 kg/m 2 compared with patients of normal weight (47% vs. 28%, p = 0.068). Conclusions: BMI ≥25 kg/m 2 may be a significant risk factor for cardiac toxicity after RT for left-sided breast cancer, possibly because of more frequent deep set-up errors resulting in the inclusion of additional heart in the RT fields. Further study is necessary to better understand the impact of patient-specific factors and set-up errors on the development of RT-induced perfusion defects.

Impact of patient-specific factors, irradiated left ventricular volume, and treatment set-up errors on the development of myocardial perfusion defects after radiation therapy for left-sided breast cancer.

X. Yu

Papers

The incidence and functional consequences of RT-associated cardiac perfusion defects

Radiation-induced lung injury.

Dosimetric and clinical predictors for radiation-induced esophageal injury

Prospective assessment of radiotherapy-associated cardiac toxicity in breast cancer patients: analysis of data 3 to 6 years after treatment.

Impact of patient-specific factors, irradiated left ventricular volume, and treatment set-up errors on the development of myocardial perfusion defects after radiation therapy for left-sided breast cancer.